In patients with diffuse lung metastases and no systemic chemotherapy option, therapeutic alternatives are scarce.
Locoregional transcatheter treatment of lung tumors found considerable interest in the 1950s and 1960s, with a number of groups delivering intra-arterial chemotherapy via the bronchial arteries. Japanese groups replicated these approaches in the 1990s in an attempt to downstage locally unresectable stage III bronchial carcinoma. Results of small single-arm cohorts were published, but a transition of these activities to phase III is still missing.
Metastatic disease of the lung is a frequent finding in solid tumors. Aggressive treatment of lung tumors by resection or ablation has been established in various entities, such as colorectal cancer, melanoma, renal cancer, sarcoma, non-small cell lung cancer (NSCLC) and others. However, in multiple lesions surgical resection is limited by the residual lung capacity.
Local ablation such as by radiofrequency ablation (RFA) is well established in solitary lesions but rarely applicable if the lesion number is greater than three or the lesion diameter is larger than 3 cm. Stereotactic irradiation or CT-guided brachytherapy have demonstrated favourable results but, as is RFA, are limited to small lesion numbers and cannot be applied in diffuse lung metastases.
Some authors have described the treatment of lung malignancies by chemoembolization (TPCE) via the pulmonary artery. However, despite reports of moderate response rates the approach remains controversial. Image data suggest that metastases might not be supplied by pulmonary arteries but rather by the bronchial artery, and lipiodol from TPCE may even be visualized in the pulmonary parenchyma only, sparing the targeted metastases. Arterial chemoperfusion via the bronchial artery has raised strong interest in the 1960s in attempts to improve the cytotoxic therapy of lung malignancies.
Jonas at al. [Jonas A M, Carrington C B (1969) Vascular patterns in primary and secondary pulmonary tumors in the dog. Am J Pathol 56(1):79-95] published data for in vivo and postmortem injection of contrast dye, gelatin, or vinylite-corrosion cast in dogs with both primary and secondary lung malignancies. All casts and the in vivo injections revealed proliferated or increased calibers of bronchial arteries supplying 100% of the primary or secondary malignancies identified. Bronchial to pulmonary artery anastomoses were not found. These results have been reproduced in a number of case reports or small cohorts in humans. It should nevertheless be noted that even though each lung malignancy displayed a bronchial artery to supply its gross mass, the tumor margin in some instances displayed a growth pattern, such as “cancerous pneumonia,” into alveolar lumen with septa still intact. In this situation, a pulmonary artery supply to the tumor margin was demonstrated. In support of these results, a recent perfusion study has demonstrated a dual perfusion pattern of primary lung cancer in 13 patients with the central bronchial perfusion being dominant with moderate dependency on tumor size, i.e., the larger the tumor, the stronger the dominance of the bronchial artery for tumor perfusion.
Despite the many refinements in surgical techniques, the increase in knowledge around the blood supply to carcinomas in the lung and new targeted pharmacologic agents, lung tumors remain one of the most lethal cancers. Adjuvant treatment options are limited and there is a clear need for further research and new treatment approaches in this field.
Selective internal radiation therapy (SIRT), which is the intra-arterial delivery of radioactive microparticles to tumours, has an established therapeutic role in the management of inoperable primary and metastatic liver tumours. However, the utility of SIRT for the management of LCC remains largely unexplored and unknown in light of whether the same endovascular principles may be deployed and more relevantly what dose is required in cases of lung trauma and in the management of a range of benign and malignant conditions.
It is against this background that the present invention has been developed.